Role of immunohistochemical markers in predicting progression of dysplasia to advanced neoplasia in patients with ulcerative colitis

Background: Although dysplasia is thought to be the precursor lesion in the development of colitis-associated colorectal cancer (CRC), a significant proportion of patients with ulcerative colitis (UC) and low-grade (LGD) or indefinite (IND) dysplasia remain cancer-free during endoscopic follow-up. There is a need for biomarkers that predict neoplastic progression. We studied the value of a series of immunohistochemical markers in UC patients with flat LGD or IND with regard to neoplastic progression. Methods: Tissue samples were collected from 12 UC patients (six flat LGD, six IND) without progression and from 10 UC patients (eight flat LGD, two IND) with documented progression to HGD and/or CRC during a median of 25 and 23 months of colonoscopic follow-up, respectively. Immunohistochemistry using monoclonal antibodies was performed for p53, CD44, Ki67, AMACR, beta-catenin, cyclin D1, p21, and ALDH. Positive and negative staining patterns were compared for progression to advanced neoplasia. Results: When patients showed coexpression of p53 and AMACR, 6/7 patients (86%) developed advanced neoplasia, compared to 4/15 patients (27%) without p53/AMACR coexpression (P = 0.02). Patients with p53/AMACR coexpression developed advanced neoplasia in a time period of 19 months (median, range 1-101) compared to 80 months (median, range 8-169) in patients without p53/AMACR coexpression (P = 0.14). Interestingly, in three patients with progression and previous dysplasia-negative biopsies, two out of three biopsies were p53-positive a median of 12 months (range 10-14) before the LGD/IND diagnosis. Conclusions: This study suggests a role for p53/AMACR coexpression as a potential marker of neoplastic progression in patients with UC